Cellular and behavioral neurobiology of alcohol: receptor-mediated neuronal processes.
ABSTRACT Ethanol can be viewed as a receptor modulator, selectively altering neurochemical processes in discrete regions of the CNS. The actions of ethanol at two inotropic receptor systems, gamma-aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) glutamate receptors, are highlighted in this review. In addition, evidence is presented and discussed concerning the possible effects of ethanol that arise from interactions between these two receptor systems, the interactions of ethanol with phosphorylation states of receptor proteins and with metabotropic receptor systems.
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ABSTRACT: Alcohol is a rich drug affecting both the γ-amino butyric acid (GABA) and glutamatergic neurotransmitter systems. Recent findings from both modelling and pharmacological manipulation have indicated a link between GABAergic activity and oscillations measured in the gamma frequency range (30-80 Hz), but there are no previous reports of alcohol's modulation of gamma-band activity measured by magnetoencephalography (MEG) or electroencephalography (EEG). In this single-blind, placebo-controlled crossover study, 16 participants completed two study days, one in which they consumed a dose of 0.8 g/kg alcohol, and the other a placebo. MEG recordings of brain activity were taken before and after beverage consumption, using visual grating and finger abduction paradigms known to induce gamma-band activity in the visual and motor cortices respectively. Time-frequency analyses of beamformer source reconstructions in the visual cortex showed that alcohol increased peak gamma amplitude and decreased peak frequency. For the motor task, alcohol increased gamma amplitude in the motor cortex. These data support the notion that gamma oscillations are dependent, in part, on the balance between excitation and inhibition. Disruption of this balance by alcohol, through increasing GABAergic inhibition at GABAA receptors and decreasing glutamatergic excitation at NMDA receptors, alters both the amplitude and frequency of gamma oscillations. The findings provide further insight into the neuropharmacological action of alcohol.Neuropsychopharmacology accepted article preview online, 13 March 2014; doi:10.1038/npp.2014.58.Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 03/2014; DOI:10.1038/npp.2014.58 · 8.68 Impact Factor
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ABSTRACT: Prolonged alcohol consumption is associated with a variety of neuropsychiatric conditions, including the dense amnesic disorder known as Korsakoff's syndrome. Korsakoff's syndrome is frequently diagnosed in alcoholics after an episode of acute thiamin deficiency. The accepted view within the medical literature is that the etiology of this disorder lies in thiamin deficiency or Wernicke's encephalopathy. However, examination of the published reports of pure thiamin deficiency unaccompanied by chronic and excessive consumption of alcohol shows that, in this group of patients, the rate of progression to Korsakoff's syndrome is low. This result suggests that the memory impairments associated with alcohol-related brain damage cannot be attributed to thiamin deficiency alone. The etiology of alcohol-related cognitive impairments such as Korsakoff's syndrome is still poorly understood but several lines of evidence suggest multiple causal factors interact to produce deficits in performance. Animal models that manipulate only a single putative etiological factor are unlikely to elucidate the multiple influences that lead to Korsakoff's syndrome. A study of the natural history of alcohol-related brain damage is needed that will allow an assessment of individual risk factors and their interactions.Alcohol 01/1999; 19(1). DOI:10.1016/S0741-8329(99)00027-0 · 2.04 Impact Factor
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ABSTRACT: Alcohol withdrawal syndrome is associated with increased central N-methyl-D-aspartate (NMDA) glutamate transmission. Medications that reduce glutamate release or block NMDA overactivation have shown efficacy for treating alcohol withdrawal syndrome. Dextromethorphan (DXM), a widely used antitussive drug, is a low-affinity, noncompetitive NMDA antagonist with potential neuroprotective properties. This study, using a randomized, double-blind, placebo-controlled study design, examined the benefit of DXM in the management of acute alcohol withdrawal. Alcohol-dependent patients admitted for detoxification treatment and experiencing moderate alcohol withdrawal, as measured by a score greater than 10 on the revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), were randomly assigned to receive either DXM 360 mg/d or an identical placebo for 7 days in a double-blind manner. All subjects received a concurrent dose of lorazepam 2 mg along with the initial administration of DXM or placebo and were given additional lorazepam (1 mg) as a rescue medication according to the symptom-triggered detoxification protocol. Outcome measures consisted of the mean total dose of lorazepam received, the sequential scores on the CIWA-Ar, and craving assessed by the Obsessive-Compulsive Drinking Scale. Forty subjects completed the study, 18 in the DXM group and 22 in the placebo group. We found that compared with placebo, DXM use was not associated with lower lorazepam doses to control alcohol withdrawal symptoms. The progression in CIWA-Ar and Obsessive-Compulsive Drinking Scale scores was also comparable between the 2 groups. Our preliminary results do not support the efficacy of high-dose DXM in reducing the need of benzodiazepines to treat withdrawal symptoms in alcohol-dependent patients.Journal of clinical psychopharmacology 12/2013; DOI:10.1097/JCP.0000000000000052 · 5.09 Impact Factor